A new family of retroviruses with potential as etiologic agents in the cause of human malignancies has been discovered. HTLV-I has been associated with a distinct form of T-cell leukemia/lymphoma, ATL. HTLV-III is a likely candidate as the etiologic agent of the acquired immunodeficiency syndrome (AIDS) associated with malignant Kaposi's sarcoma, and certain forms of non-Hodgkin's lymphoma. The purpose of this project is to employ epidemiologic techniques to characterize the relationship of this class of virus to human malignancy. Results of these studies document the close link between HTLV-I and ATL, its worldwide distribution, and tendency to be tightly clustered in close association with endemic HTLV-I infection. Modes of spread include sexual and household factors and possibly vector-borne transmission. Genetic susceptibility is also suggested. An indirect etiologic mechanism of leukemogenesis is also suggested for HTLV-I in B-CLL, and for HTLV-III in some B-cell lymphomas. Within the context of AIDS, Section personnel have pioneered studies of several AIDS high-risk cohorts followed longitudinally since the very beginning of the AIDS epidemic. Results of these studies document that depressed T-4 cells in healthy at-risk individuals appear to be an outcome of exposure to the AIDS agent. Thus, sexual liaison by persons from intermediate risk areas with persons from high risk areas is associated with this abnormality. In high risk areas the number of sexual partners is the major risk factor. Receptive anal intercourse is the major mode for transmission. Investigations of HTLV-III in these cohorts documents an overriding association for various outcomes including AIDS, lesser AIDS, lymphadenopathy syndrome, and altered R-4 cells with this exposure. Furthermore, HTLV-III infection antedated these outcomes in all cases documenting that it is not just another passenger virus. These results lay the foundation for undertaking in-depth analytic studies of these retrovirus exposures to better quantify these risks and the cofactors which determine the clinical outcome of exposure.